Enhanced antitumor effects by combination gene therapy using MDR1 gene shRNA and HSV1-tk in a xenograft mouse model
Enhanced antitumor effects by combination gene therapy using MDR1 gene shRNA and HSV1-tk in a xenograft mouse model
复制标题
DOI：
10.1016/j.canlet.2009.10.002
复制
发表时间：
2010-05-01
期刊：
影响因子：
9.7
通讯作者：
Lee, Jaetae
中科院分区：
文献类型：
--
作者：
Lee, Sang-Woo;La Lee, You;Lee, Jaetae
使用一种新的治疗载体含有HSV 1-胸苷激酶（HSV 1-tk）和一个短发夹RNA的MDR 1基因（shMDR）的建议。我们研究了体内结肠癌小鼠模型的抗肿瘤作用，并通过一系列非侵入性成像评估了治疗反应。用更昔洛韦和多柔比星的双重治疗组小鼠的shMDR-TK表达（MTKG）肿瘤显示大小减小，而单一治疗组小鼠的肿瘤显示中度增加（p < 0.05）。对于单药或双药治疗组小鼠，MTKG与亲本HCT-15肿瘤的I-131-5-碘-2 '-氟-2'-脱氧-1-β-D-阿拉伯呋喃糖基尿嘧啶（FIAU）摄取比随着治疗进展而降低，而对照组小鼠的FIAU摄取比逐渐升高。本研究证实了与单一治疗方法相比，联合基因治疗的抗肿瘤效果增强，并提供了治疗反应监测的潜力。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The use of a novel therapeutic vector containing HSV1-thymidine kinase (HSV1-tk) and a short hairpin RNA for the MDR1 gene (shMDR) was proposed previously. We investigated the antitumor effects in an in vivo mouse model of colon cancer and assessed treatment response by serial non-invasive imaging. shMDR-TK expressing (MTKG) tumors for the dual therapy group mice with ganciclovir and doxorubicin showed a decrease in size, while tumors in the single therapy group mice showed a moderate increase (p < 0.05). The I-131-5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) uptake ratio of MTKG-to-parent HCT-15 tumors decreased as treatment progressed for single or dual therapy group mice, while that of the control group mice increased gradually. This study demonstrates the enhanced antitumor effects with combination gene therapy compared with a single therapeutic approach, and provides the potential of therapeutic response monitoring. (C) 2009 Elsevier Ireland Ltd. All rights reserved.